AB0138 CHARACTERIZATION OF SERUM CYTOKINE PROFILE IN PATIENTS WITH ACTIVE LUPUS NEPHRITIS
Authors: Z. Rahme, M. Gatto, A. Ghirardello, C. Cruciani, F. Pettorossi, A. Zaramella, C. Franco, A. Doria
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Cytokines (CKs) are known to play a role in the pathogenesis of lupus nephritis (LN), yet their role as biomarkers is still debated. <h3>Objectives</h3> To describe the CKs picture in patients with active LN and to assess possible clinical correlates in LN course. <h3>Methods</h3> A prospective cohort study including patients with active biopsy-proven LN was performed. Serum CKs were assessed at the time of diagnosis and at 3 subsequent time points (3, 6 and 12 months) during follow-up. Clinical and serological data were collected for further analysis. BLyS (B Lymphocyte stimulator) and interleukin (IL)-37 were measured by ELISA assays (Quantikine BAFF, R&amp;D, USA, detection limit DL 0.02 ng/mL; IL37 ELISA kit, Adipogen, Swizerland, DL 0.001 ng/mL), IL-2, IL-10, IL-17A and IL-18 (pg/mL) by Luminex multiplex assay (Millipore, USA, DL 0.6 pg/mL for all), according to the manufacturers' instructions. Measurements for IL-37 and BLyS were matched with sera of sex- and age- matched healthy subjects (HC). Mann-Whitney test was used for comparisons between two independent groups, Wilcoxon log-rank test for paired comparisons at different time points, Spearman's correlation coefficient for associations between CK and between CK and clinical features. <h3>Results</h3> Twenty-seven patients with active LN (mean±SD age 41.75±14.74, 78.8% women) were included for initial CK analysis at the time of LN activity. At baseline (T0), BLyS levels were significantly increased in LN compared with HC (median [range], 1.107 [0.326-4.00] vs. 0.563 [0.265-1.409]; p&lt;0.0001); IL-37 was significantly reduced in LN compared with HC (median [range] 0.016 [0.001-0.251] vs. 0.056 [0.001-1.147]; p = 0.0185). At T0, median (range) levels of IL-2, IL-10, IL-17A and IL-18 were: IL-2 0.640 (0-37.82), IL-10 2.60 (0-106.86), IL-17A 2.10 (0-138.20), IL-18 243.10 (28.20-950.30). The longitudinal association study between CK levels of the entire cohort revealed a trend of inverse correlation between IL-37 and BLyS (r=-0.281, p=0.06) and a direct correlation between BLyS and IL-18 (r=0.330, p=0.04) and between IL-2 and IL-17A (r=0.470, p&lt;0.001) (Figure 1). A subset of 17 patients (70.6% F, mean age at renal flare 34.3±18.6y, mean duration of disease at the time of renal flare 4.99±8.94y, caucasian ethnicity n=14, 82.3%), was followed-up prospectively: 7 (41.18%) had biopsy-proven (III-IV class) proliferative glomerulonephritis. Proteinuria at T0 was 2.19±1.35 g/24h. All patients were treated with pulsed glucocorticoids (GCS, 750-2500 mg) followed by oral GCS (0.3-0.5mg/kg/day prednisone equivalent) and immunosuppression1. Higher titres of IL-18 were present in the sera of patients with proliferative forms of LN (p=0.053) and with a higher SLEDAI-2K score at T0 (p=0.0759). A significant correlation was found between IL-2, and to a lesser extent of IL-17, with anti-dsDNA antibodies (IL2: r=0.6098, p=0.0094; IL17: r=0.4591, p=0.0638). High levels of IL-17 correlated with lower C3 at T0 (r=-0.5085, p=0.0372). No significant longitudinal changes in CKs levels nor correlation with clinical features were observed. <h3>Conclusion</h3> Patients with proliferative LN and higher SLEDAI-2K scores displayed higher levels of IL-18, thus supporting IL-18 likely role in the pathogenesis of LN. We documented a correlation between IL2 and higher titres of anti-dsDNA antibodies and an inverse correlation between IL-17 and C3 at baseline, suggesting a contribution of CKs to LN onset. Our study was limited by the small sample size, limiting retrieval of significant data on CK levels and clinical-laboratoristic changes at different time points, demanding further studies. <h3>References</h3> [1]Fanouriakis A, et al 2019 Ann Rheum Dis 2019;78:736-745 [2]Mende, et al. Front Immunol vol. 9 1250. 7 Jun. 2018, doi:10.3389/fimmu.2018.01250 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.